search
Back to results

Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma

Primary Purpose

Diffuse Large B-Cell Lymphoma (DLBCL), Primary Mediastinal Large B-cell Lymphoma, Burkitt Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EPOCH
Rituximab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma (DLBCL) focused on measuring Primary Mediastinal B-Cell Lymphoma, CD20 +, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, De Novo

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell lymphoma. Diagnosis confirmed by staff of the Hematopathology Section, Laboratory of Pathology, NCI. Tissue blocks from patients treated in extramural sites must be forwarded to the NCI for analysis of bcl-2 by IHC and other markers within 1 month of study entry. Patients greater than or equal to 12 years old. Stage and Prognosis of Patients: Any stage for MGZL and PMBL. No prior systemic chemotherapy. Patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome). HIV negative. Not pregnant or nursing. Adequate major organ function [in adults: serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 ml/min; and in children serum CR less than or equal to age-adjusted normal (age 12 to 15 maximum serum creatinine 1.2 mg/dl and age greater than 15 maximum serum creatinine 1.5 mg/dl); bilirubin less than 1.5 mg/dl; ANC greater than 1,000 and platelets greater than 100,000) unless impairment is due to organ involvement by lymphoma or immune-mediated mechanism caused by lymphoma. No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If MUGA is obtained, the LVEF should exceed 40%. No other serious concomitant medical illnesses or uncontrolled active infection that would jeopardize the patient's ability to receive the regimen with reasonable safety. No history of unrelated (non-lymphomatous) neoplasms within past 5 years other than non-melanoma skin cancer or in-situ cancer. Ability to give informed consent.

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A

Arm Description

EPOCH + Rituximab every 3 weeks for 6 cycles.

Outcomes

Primary Outcome Measures

Overall response and PFS
The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) patients may experience an improved progression free survival with EPOCH-R compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival.

Secondary Outcome Measures

Safety and Toxicity
the proportion of patients with adverse events leading to discontinuation of therapy

Full Information

First Posted
November 3, 1999
Last Updated
October 18, 2023
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00001337
Brief Title
Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma
Official Title
Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 4, 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 8, 1993 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. EPOCH: Etoposide, VP-16, NSC-141540; Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629.
Detailed Description
Background: The treatment of the intermediate and aggressive non-Hodgkin's lymphomas in adults and children commonly induces complete responses in a sizable fraction of the treated population, and about 2/3 of the complete responders appear to have prolonged disease-free survival. The present study assesses the activity and tolerability in previously untreated patients of a regimen of EPOCH infusional chemotherapy given intensively with G-CSF support. Objectives: Primary: Assess complete response (CR) and progression-free survival (PFS) of dose-adjusted EPOCH-Rituximab (DA-EPOCH-R) with G-CSF in agressive B-cell lymphomas. Eligibility: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma (MGZL) and primary mediastinal B cell lymphoma (PMBL). Patients greater than or equal to 12 years old. Any Stage for PMBL and MGZL. No prior systemic chemotherapy. HIV negative. Design: This study will estimate the complete response rate of a group of previously untreated patients and the extent to which EPOCH infusional drug delivery accompanied by a hematopoietic growth factor can increase the dose intensity of treatment. Patients receive prednisone orally for 5 days, a 96 hour infusion of vincristine, doxorubicin, and etoposide, and a bolus of cyclophosphamide on day 5. Cycles are repeated every 21 days for a total of 6-8 cycles. Patients with CD20 expressing tumors (i.e. mature B-cell lymphomas) will also receive rituximab, the humanized monoclonal antibody against the CD20 receptor on day 1 of each cycle. A total of 348 patients will be enrolled on this protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma (DLBCL), Primary Mediastinal Large B-cell Lymphoma, Burkitt Lymphoma, Anaplastic Large-Cell Lymphoma, Gray Zone Lymphoma
Keywords
Primary Mediastinal B-Cell Lymphoma, CD20 +, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, De Novo

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
348 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
EPOCH + Rituximab every 3 weeks for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
EPOCH
Intervention Description
Combination chemotherapy given with Rituximab (EPOCH-R) IV every 3 weeks for 6 cycles.
Intervention Type
Biological
Intervention Name(s)
Rituximab
Intervention Description
Rituximab given on Day 1 of combination chemotherapy (EPOCH-R) every 3 weeks for 6 cycles.
Primary Outcome Measure Information:
Title
Overall response and PFS
Description
The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) patients may experience an improved progression free survival with EPOCH-R compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival.
Time Frame
Time of progression
Secondary Outcome Measure Information:
Title
Safety and Toxicity
Description
the proportion of patients with adverse events leading to discontinuation of therapy
Time Frame
Initiation of study drug until 30 days after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell lymphoma. Diagnosis confirmed by staff of the Hematopathology Section, Laboratory of Pathology, NCI. Tissue blocks from patients treated in extramural sites must be forwarded to the NCI for analysis of bcl-2 by IHC and other markers within 1 month of study entry. Patients greater than or equal to 12 years old. Stage and Prognosis of Patients: Any stage for MGZL and PMBL. No prior systemic chemotherapy. Patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome). HIV negative. Not pregnant or nursing. Adequate major organ function [in adults: serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 ml/min; and in children serum CR less than or equal to age-adjusted normal (age 12 to 15 maximum serum creatinine 1.2 mg/dl and age greater than 15 maximum serum creatinine 1.5 mg/dl); bilirubin less than 1.5 mg/dl; ANC greater than 1,000 and platelets greater than 100,000) unless impairment is due to organ involvement by lymphoma or immune-mediated mechanism caused by lymphoma. No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If MUGA is obtained, the LVEF should exceed 40%. No other serious concomitant medical illnesses or uncontrolled active infection that would jeopardize the patient's ability to receive the regimen with reasonable safety. No history of unrelated (non-lymphomatous) neoplasms within past 5 years other than non-melanoma skin cancer or in-situ cancer. Ability to give informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark J Roschewski, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2580468
Citation
Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. doi: 10.7326/0003-4819-102-5-596.
Results Reference
background
PubMed Identifier
1682280
Citation
Lai GM, Chen YN, Mickley LA, Fojo AT, Bates SE. P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991 Nov 11;49(5):696-703. doi: 10.1002/ijc.2910490512.
Results Reference
background
PubMed Identifier
46388
Citation
DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. doi: 10.1016/s0140-6736(75)91142-3.
Results Reference
background
PubMed Identifier
34432874
Citation
Miljkovic MD, Melani C, Pittaluga S, Lakhotia R, Lucas N, Jacob A, Yusko E, Jaffe ES, Wilson WH, Roschewski M. Next-generation sequencing-based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL. Blood Adv. 2021 Oct 26;5(20):4198-4210. doi: 10.1182/bloodadvances.2020003679.
Results Reference
derived
PubMed Identifier
30125215
Citation
Kurtz DM, Scherer F, Jin MC, Soo J, Craig AFM, Esfahani MS, Chabon JJ, Stehr H, Liu CL, Tibshirani R, Maeda LS, Gupta NK, Khodadoust MS, Advani RH, Levy R, Newman AM, Duhrsen U, Huttmann A, Meignan M, Casasnovas RO, Westin JR, Roschewski M, Wilson WH, Gaidano G, Rossi D, Diehn M, Alizadeh AA. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2018 Oct 1;36(28):2845-2853. doi: 10.1200/JCO.2018.78.5246. Epub 2018 Aug 20.
Results Reference
derived
PubMed Identifier
29748435
Citation
Melani C, Advani R, Roschewski M, Walters KM, Chen CC, Baratto L, Ahlman MA, Miljkovic MD, Steinberg SM, Lam J, Shovlin M, Dunleavy K, Pittaluga S, Jaffe ES, Wilson WH. End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making. Haematologica. 2018 Aug;103(8):1337-1344. doi: 10.3324/haematol.2018.192492. Epub 2018 May 10.
Results Reference
derived
PubMed Identifier
25024303
Citation
Wilson WH, Pittaluga S, Nicolae A, Camphausen K, Shovlin M, Steinberg SM, Roschewski M, Staudt LM, Jaffe ES, Dunleavy K. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014 Sep 4;124(10):1563-9. doi: 10.1182/blood-2014-03-564906. Epub 2014 Jul 14.
Results Reference
derived
PubMed Identifier
24224624
Citation
Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. doi: 10.1056/NEJMoa1308392.
Results Reference
derived
PubMed Identifier
23574119
Citation
Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. doi: 10.1056/NEJMoa1214561.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_1993-C-0133.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma

We'll reach out to this number within 24 hrs